Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents

BACKGROUND: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents. METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards. RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T(5) (MIC(BS, EC) = 24.7 µM, MIC(PA), (CA) = 12.3 µM) and T(17) (MIC(AN) = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MIC(Cipro) = 18.1 µM, MIC(Amo) = 17.1 µM) and fluconazole (MIC(Flu) = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T(2) (IC(50) = 34.83 µg/ml) and T(3) (IC(50) = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC(50) = 35.44 µg/ml). Compounds T(3) (IC(50) = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC(50) = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T(2) (IC(50) = 3.84 μM) and T(7) (IC(50) = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC(50) = 25.36 μM).